Roles of the postsynaptic adhesion molecule NGL-2 in the regulation of synaptic plasticity and behavior시냅스 접착 단백질 NGL-2에 의한 시냅스 가소성 및 행동 조절에 관한 연구

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dc.contributor.advisorKim, Eunjoon-
dc.contributor.advisor김은준-
dc.contributor.authorUm, Seung Min-
dc.date.accessioned2019-08-22T02:43:25Z-
dc.date.available2019-08-22T02:43:25Z-
dc.date.issued2018-
dc.identifier.urihttp://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=827907&flag=dissertationen_US
dc.identifier.urihttp://hdl.handle.net/10203/264768-
dc.description학위논문(박사) - 한국과학기술원 : 생명과학과, 2018.8,[iv, 80 p. :]-
dc.description.abstractNGL-2/Lrrc4 is one of the postsynaptic adhesion molecules that contains leucine rich repeats (LRRs), a shared feature of LRR proteins such as LTRRM and SALM. NGL-2 intracellularly interacts with the postsynaptic scaffolding protein PSD-95 and trans-synaptically binds to the presynaptic adhesion molecule Netrin-G2. Previous studies have reported that NGL-2 is expressed in a layer-specific manner in the brain and regulates diverse neurophysiological functions including excitatory synapse development and synaptic transmission. Moreover, recent bioinformatics studies of neuropsychiatric disorders such as autism spectrum disorder (ASD) and schizophrenia have strongly associated mutations of NGL2/LRRC4 in these diseases through approaches including whole exome and genome sequencing. The function of NGL-2, however, remains largely unknown from the behavioral and physiological perspectives. Here, my study show that NGL-2 regulates NMDA receptor-dependent synaptic transmission and plasticity and social and repetitive behaviors based on the data from Ngl$2^{-/-}$ mice that lack NGL-2 proteins. The defects in social interaction and repetitive behaviors, two core symptoms of ASD, were successfully rescued by the partial NMDA receptor agonist D-cycloserine. In addition, D-cycloserine improved abnormal NMDAR function and synaptic plasticity in these mice. Together, my study has found novel functions of NGL-2 in regulating NMDAR receptors, a core component of excitatory synaptic transmission, and critical brain function including sociability, cognition, and learning and memory. This study also highlights the importance of NGL-2 in neuropsychiatric disorders, and suggests abnormal NMDAR function might represent a therapeutic target for related disorders.-
dc.languageeng-
dc.publisher한국과학기술원-
dc.subjectSynaptic Plasticity▼aNMDAR function▼aASD▼aSchizophrenia▼aSynaptic cell adhesion molecule-
dc.subjectNMDA 수용체▼a시냅스 가소성▼a자폐스펙트럼질환▼a정신분열질환▼a접착 단백질-
dc.titleRoles of the postsynaptic adhesion molecule NGL-2 in the regulation of synaptic plasticity and behavior-
dc.title.alternative시냅스 접착 단백질 NGL-2에 의한 시냅스 가소성 및 행동 조절에 관한 연구-
dc.typeThesis(Ph.D)-
dc.identifier.CNRN325007-
dc.description.department한국과학기술원 :생명과학과,-
dc.contributor.alternativeauthor엄승민-
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